Influence of flow on mucosal-to-arterial carbon dioxide difference

Intramucosal-to-arterial carbon dioxide difference (the so-called PCO2 [partial carbon dioxide tension] gap) remains largely unaltered during decreased oxygen delivery, if the latter is reduced as flow is maintained. In this condition (hypoxic hypoxia or anaemic hypoxia), the PCO2 gap fails to mirror intestinal tissue dysoxia. Results from several experiments have demonstrated that blood flow is the main determinant of PCO2 gap. Gastrointestinal tonometry is clearly a useful indirect method for monitoring perfusion, but it has rather limited value in detecting anaerobic metabolism when blood flow is preserved. These considerations render it very unlikely that PCO2 may dramatically increase (or that intramucosal pH may decrease) in any hypoxic state with preserved flow.

In the present issue of Critical Care, Dubin and collaborators [1] report the results of a study in which they tested the hypothesis that intramucosal-to-arterial carbon dioxide difference (the so-called PCO2 [partial carbon dioxide tension] gap) may remain unaltered during dysoxia (a state in which oxygen delivery [DO2] is insufficient to sustain oxygen demand) because DO2 is reduced when flow is maintained. In order to achieve this and to avoid the confounding effects of low flow, they produced hypoxaemia with preserved intestinal flow. The PCO2 gap obtained in this condition (hypoxic hypoxia [HH]) was compared with that obtained in ischaemic hypoxia (IH).

This work conducted in sheep is an important confirmatory study of our previous studies that dealt with differential effects of IH and HH on PCO2 gap [2,3]. In those earlier reports, we clearly demonstrated that dog limb venous-to-arterial carbon dioxide gap [2] increased greatly in IH (approximately 17 mmHg at critical DO2 and approximately 27 mmHg at maximal DO2) and remained almost unaltered in HH (10 mmHg) [2]; and that pig gastrointestinal mucosal-to-arterial carbon dioxide gap increased to a greater extent in IH (maximal value approximately 50 mmHg) than in HH (maximal value approximately 30 mmHg) [3]. In the range of DO2 values below the critical level, increases in PCO2 gap were smaller in HH than in IH, although similar decreases in DO2 were achieved. Dependency on oxygen supply may therefore develop in the absence of large increases in tissue PCO2 during hypoxia. We concluded that these experimental findings were important in interpreting moderate increases in intestinal mucosal PCO2, because mucosal-to-arterial carbon dixoide difference (ΔPCO2) may underestimate the extent of oxygen supply limitation [3].

It is important to emphasize that, if studies are to be valid, those investigating oxygen supply dependency must consider important experimental conditions, which were clearly present in our previous studies [2,3]. The first condition is that the lowest DO2 value reached by the end of the decreased DO2 period must clearly go beyond the critical DO2. The second is that the magnitude of decreased DO2 must be similar in both IH and HH. Although the first condition appeared to be met in the report from Dubin and coworkers [1], the second one did not because the lowest DO2 reached at the intestinal level was clearly different between the groups (about 20 ml/kg per min in IH and about 40 ml/kg per min in HH). ΔPCO2 in IH increased to a maximum of about 40 mmHg, which is lower than the approximately 50 mmHg achieved in our work [3]. This suggests that the DO2 challenge in the experiments reported by Dubin and coworkers was less severe than that in ours. Although this is unfortunate, it does not prevent that study from confirming that ΔPCO2 fails to mirror intestinal tissue dysoxia and that blood flow is the main determinant of ΔPCO2. Tonometry is clearly a useful method for monitoring perfusion, but it has rather limited value in detecting anaerobic metabolism when blood flow is preserved.

The latter point was further confirmed by Dubin and collaborators during anaemic hypoxia, and results were presented recently at the 15th Annual Congress of the European Society of Intensive Care Medicine, in Barcelona [4]. In that new set of experiments conducted in sheep, ΔPCO2 did not increase when DO2 was lowered below its critical value during progressive severe anaemia.

All together, the four studies [1,2,3,4] demonstrate the following: that ΔPCO2 cannot be taken as a surrogate marker of dysoxia; and that increased ΔPCO2 cannot occur when flow is constant. These considerations render it very unlikely that ΔPCO2 may dramatically increase (or that intramucosal pH may decrease) during normal flow [5]; incomplete experimental information needs to be considered in that particular case to explain apparent contradictory results. For example, flow heterogeneity may clearly complicate interpretation of results; high flow coexisting with islands of low flow may mimic the coexistence of a high carbon dioxide gap with normal or even high-flow oxygenation [6]. As mentioned by Dubin and coworkers [1], impaired villous microcirculation has been suggested [6] to be the causal phenomenon in cytopathic hypoxia [5], a situation in which intramucosal acidosis should theoretically arise with preserved tissue perfusion.